[186Re]-labeled mouse and chimeric monoclonal antibody 323/A3: a comparison of the efficacy in experimental human ovarian cancer.
We have investigated whether [186Re]-labeled chimeric monoclonal antibody 323/A3 (MAb c-323/A3) is as effective as [186Re]-labeled mouse 323/A3 (m-323/A3) in the growth inhibition of human ovarian cancer xenografts OVCAR-3 and FMa. [186Re] was conjugated to MAbs with the use of the chelate S-benzoylmercaptoacetyltriglycine (S-benzoyl-MAG3). The maximum number of metal-MAG3 groups that could be conjugated to one MAb molecule accepting a minimal initial increase of the blood clearance (15%) was 8.5 and 2.9 for c-323/A3 and m-323/A3, respectively. With these molar ratios the immunoreactivity of both MAbs was maintained. An inverse relationship was observed between the protein dose of c-323/A3 and its blood clearance. Both [186Re]-c-323/A3 and [186Re]-m-323/A3 were comparable in the inhibition of the tumor growth when higher protein doses were used. Together with the expected lower immunogenicity, our results imply that c-323/A3 is preferable for use in [186Re]-radioimmunotherapy in ovarian cancer patients.
Kievit
E
E
Department of Medical Oncology, University Hospital Vrije Universiteit, Amsterdam, The Netherlands.
van Gog
F B
FB
Schlüper
H M
HM
van Dongen
G A
GA
Pinedo
H M
HM
Boven
E
E
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002614:Chelating Agents / Q000737:chemistry; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D005260:Female; D005998:Glycine / Q000031:analogs & derivatives / Q000737:chemistry; D006801:Humans; D000922:Immunotoxins / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007526:Isoelectric Point; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000532:radiotherapy* / Q000628:therapy*; D016499:Radioimmunotherapy; D011868:Radioisotopes; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D012211:Rhenium; D014018:Tissue Distribution; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D002614:Chelating Agents; D000922:Immunotoxins; D011868:Radioisotopes; D011993:Recombinant Fusion Proteins; D012211:Rhenium; C111010:S-benzoylmercaptoacetyltriglycine; D005998:Glycine